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| ID | Type | Description | Link |
|---|---|---|---|
| 2004-001540-71 | EudraCT Number |
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Primary Outcome Measures:
The primary endpoint was the time to onset of symptom relief of the first attack in the double blind phase. H0: λ icatibant/λ tranexamic acid =1 versus H1: λ icatibant/λ tranexamic acid ≠1 Where: λ icatibant refers to the hazard rate under icatibant and λ tranexamic acid refers to the hazard rate under tranexamic acid.
Secondary Outcome Measures:
This was a Phase III, randomised, double blind, double dummy, multicentre, controlled,parallel group study of a 30 mg s.c. formulation of icatibant for the treatment of patients with moderate to very severe symptoms of cutaneous and/or abdominal symptoms of HAE.
The study consisted of two parts: controlled phase and OLE phase. For the primary endpoint, Efficacy was determined by evaluating the differences in study outcomes using a Visual Analogue Scale for patients treated with icatibant and tranexamic acid.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Randomized controlled -Icatibant | Experimental | Subjects received S.C icatibant+ oral placebo Icatibant Form: solution for injection, 3 mL, 10 mg/mL Single dose: 30 mg (3 mL) Placebo Form: hard capsule Single dose: 2 capsules Frequency: 3 x 2 capsules for 2 days, taken orally, 6 to 8 hours apart |
|
| Randomized controlled-Tranexamic acid | Active Comparator | Subjects received oral Tranexamic acid+ S.C. placebo Tranexamic acid Form: over encapsulated film tablet Single dose: 1000 mg (2 capsules) Frequency: 3 x 2 capsules for 2 days, taken orally, 6 to 8 hours apart Placebo Form: solution for injection, matched to icatibant for injection Single dose: 3 mL Frequency: one subcutaneous injection in the abdominal region |
|
| Controlled Open-label / laryngeal attack | Experimental | Patients with laryngeal symptoms at the baseline were not randomised but treated with icatibant open label during the controlled phase. |
|
| Untreated patients at the baseline | Experimental | Patients who were screened and found eligible but did not experience an angioedema attack, or had an attack that was not severe enough to merit treatment while the controlled phase was ongoing were treated in the open label phase with icatibant |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Icatibant | Drug | Icatibant: a stable, synthetic decapeptide and specific BK B2 receptor antagonist. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Time to Onset of Symptom Relief. | The primary efficacy endpoint was Time to onset of symptom relief (TOSR) following treatment with either icatibant or tranexamic acid. The median time to onset of symptom relief for the icatibant group was compared to the the median time to onset of symptom relief for the tranexamic acid group. TOSR was defined as the time between time of injection to time of first documented onset of symptom relief for the three primary symptoms: cutaneous swelling, cutaneous skin, and abdominal pain. The primary symptom was based on the type of attack. For abdominal attacks, the single primary symptom was abdominal pain. For cutaneous attacks, the single primary symptom was either skin swelling or skin pain, whichever was most severe. | 2 days |
| Measure | Description | Time Frame |
|---|---|---|
| Time to Almost Complete Symptom Relief | Almost complete symptom relief was defined as a score between 0 and 10 mm on the VAS for at least three consecutive measurements for all symptoms. | 48 hours |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Study Director | Takeda | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Università degli Studi di Milano, Dipartimento di Medicina Interna | Milan | 20123 | Italy |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 17073887 | Result | Bas M, Bier H, Greve J, Kojda G, Hoffmann TK. Novel pharmacotherapy of acute hereditary angioedema with bradykinin B2-receptor antagonist icatibant. Allergy. 2006 Dec;61(12):1490-2. doi: 10.1111/j.1398-9995.2006.01197.x. No abstract available. | |
| 24111645 | Derived | Bas M, Greve J, Hoffmann TK, Reshef A, Aberer W, Maurer M, Kivity S, Farkas H, Floccard B, Arcoleo F, Martin L, Sitkauskiene B, Bouillet L, Schmid-Grendelmeier P, Li H, Zanichelli A. Repeat treatment with icatibant for multiple hereditary angioedema attacks: FAST-2 open-label study. Allergy. 2013 Nov;68(11):1452-9. doi: 10.1111/all.12244. Epub 2013 Sep 21. |
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85 patients participated in the study(36 in the icatibant group and 38 in the tranexamic acid group)3 patients with laryngeal symptoms at Baseline.8 Patients were screened and found eligible but did not experience an angioedema attack, or had an attack that was not severe enough to merit treatment while the controlled phase was ongoing
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| ID | Title | Description |
|---|---|---|
| FG000 | Randomized Controlled -Icatibant | Patients who were randomized to icatibant + Oral placebo (hard capsule matched to tranexamic acid) in the controlled phase after they had an eligible first in-study attack. |
| FG001 | Randomized Controlled-Tranexamic Acid | Patients who were randomized to received oral Tranexamic acid + S.C. placebo(solution for injection, matched to icatibant for injection) in the controlled phase after they had an eligible first in-study attack. |
| FG002 | Controlled Open-label / Laryngeal Attack | Patients with laryngeal symptoms at the baseline were not randomised but treated with icatibant open label during the controlled phase. |
| FG003 | Untreated Patients at the Baseline | Patients who were screened and found eligible but did not experience an angioedema attack, or had an attack that was not severe enough to merit treatment while the controlled phase was ongoing were treated in the open label phase with icatibant |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Controlled Phase |
| |||||||||||||
| Open Label Extension (OLE) Phase |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Randomized Controlled -Icatibant | Patients who were randomized to icatibant + Oral placebo (hard capsule matched to tranexamic acid) in the controlled phase after they had an eligible first in-study attack. |
| BG001 | Randomized Controlled-Tranexamic Acid |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Time to Onset of Symptom Relief. | The primary efficacy endpoint was Time to onset of symptom relief (TOSR) following treatment with either icatibant or tranexamic acid. The median time to onset of symptom relief for the icatibant group was compared to the the median time to onset of symptom relief for the tranexamic acid group. TOSR was defined as the time between time of injection to time of first documented onset of symptom relief for the three primary symptoms: cutaneous swelling, cutaneous skin, and abdominal pain. The primary symptom was based on the type of attack. For abdominal attacks, the single primary symptom was abdominal pain. For cutaneous attacks, the single primary symptom was either skin swelling or skin pain, whichever was most severe. | Posted | Median | Inter-Quartile Range | Hours | 2 days |
|
An AE was assigned to the controlled phase if the start date of the event was between the first treatment of the first attack and the first treatment in the OLE phase.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Controlled Phase- Icatibant (Randomized Subjects ) | Patients who were randomized to icatibant+ oral placebo in the controlled phase and experienced adverse events while participating in the controlled phase |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hereditary Angioedema | Congenital, familial and genetic disorders | MedDRA version 8.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hereditary Angioedema | Congenital, familial and genetic disorders | MedDRA version 8.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Shire | +1 866 842 5335 | ClinicalTransparency@shire.com |
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| ID | Term |
|---|---|
| D054179 | Angioedemas, Hereditary |
| ID | Term |
|---|---|
| D000799 | Angioedema |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D000081208 | Hereditary Complement Deficiency Diseases |
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| ID | Term |
|---|---|
| C065679 | icatibant |
| D014148 | Tranexamic Acid |
| ID | Term |
|---|---|
| D003509 | Cyclohexanecarboxylic Acids |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
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|
| Tranexamic Acid | Drug | over encapsulated film tablet an anti-fibrinolytic agent,is used in some European countries for the treatment of acute oedema episodes and the continuous prophylaxis of HAE. |
|
| Oral Placebo | Drug | hard capsule matched to tranexamic acid |
|
|
| S.C. Placebo | Drug | solution for injection, matched to icatibant for injection |
|
|
| 20818888 | Derived | Cicardi M, Banerji A, Bracho F, Malbran A, Rosenkranz B, Riedl M, Bork K, Lumry W, Aberer W, Bier H, Bas M, Greve J, Hoffmann TK, Farkas H, Reshef A, Ritchie B, Yang W, Grabbe J, Kivity S, Kreuz W, Levy RJ, Luger T, Obtulowicz K, Schmid-Grendelmeier P, Bull C, Sitkauskiene B, Smith WB, Toubi E, Werner S, Anne S, Bjorkander J, Bouillet L, Cillari E, Hurewitz D, Jacobson KW, Katelaris CH, Maurer M, Merk H, Bernstein JA, Feighery C, Floccard B, Gleich G, Hebert J, Kaatz M, Keith P, Kirkpatrick CH, Langton D, Martin L, Pichler C, Resnick D, Wombolt D, Fernandez Romero DS, Zanichelli A, Arcoleo F, Knolle J, Kravec I, Dong L, Zimmermann J, Rosen K, Fan WT. Icatibant, a new bradykinin-receptor antagonist, in hereditary angioedema. N Engl J Med. 2010 Aug 5;363(6):532-41. doi: 10.1056/NEJMoa0906393. |
| COMPLETED |
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| NOT COMPLETED |
|
Patients who were randomized to received oral Tranexamic acid + S.C. placebo(solution for injection, matched to icatibant for injection) in the controlled phase after they had an eligible first in-study attack. |
| BG002 | Controlled Open-label / Laryngeal Attack | Patients with laryngeal symptoms at the baseline were not randomised but treated with icatibant open label during the controlled phase. |
| BG003 | Untreated Patients at the Baseline | Patients who were screened and found eligible but did not experience an angioedema attack, or had an attack that was not severe enough to merit treatment while the controlled phase was ongoing were treated in the open label phase with icatibant |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| OG001 | Randomized Controlled-Tranexamic Acid | Patients who were randomized to received oral Tranexamic acid + S.C. placebo(solution for injection, matched to icatibant for injection) in the controlled phase after they had an eligible first in-study attack. |
|
|
|
| Secondary | Time to Almost Complete Symptom Relief | Almost complete symptom relief was defined as a score between 0 and 10 mm on the VAS for at least three consecutive measurements for all symptoms. | Posted | Median | Inter-Quartile Range | Hours | 48 hours |
|
|
|
|
| 4 |
| 36 |
| 19 |
| 36 |
| EG001 | Controlled Phase- Tranexamic Acid (Randomized Subjects) | Patients who were randomized to Tranexamic acid+ S.C. placebo in the controlled phase and experienced adverse events while participating in the controlled phase. | 1 | 38 | 16 | 38 |
| EG002 | Controlled Phase- Icatibant (Subjects w/ Laryngeal Attack) | This represents adverse events during the controlled phase that were experienced by Patients with laryngeal symptoms at the baseline and were treated with open label icatibant during the controlled phase. | 1 | 3 | 1 | 3 |
| EG003 | Open Label Extension Phase- Icatibant (Previously Randomized) | Patients who were randomized to either icatibant+ oral placebo or Tranexamic acid+ S.C. placebo in the controlled phase and experienced adverse events while participating in the open label extension phase. | 9 | 44 | 31 | 44 |
| EG004 | Open Label Extension Phase (Subjects w/ Laryngeal Attack) | This represents adverse events during the open label extension phase that were experienced by Patients with laryngeal symptoms at the baseline and got treated with open label icatibant during the controlled phase and Open label extension phase. | 1 | 2 | 1 | 2 |
| EG005 | Open Label Extension Phase(Untreated Patients at the Baseline | This represents adverse events experienced by Patients who were screened and found eligible but did not experience an angioedema attack, or had an attack that was not severe enough to merit treatment while the controlled phase was ongoing. | 0 | 8 | 4 | 8 |
| Aortic Value Sclerosis | Cardiac disorders | MedDRA version 8.1 | Systematic Assessment |
|
| Sudden Cardiac Death | General disorders | MedDRA version 8.1 | Systematic Assessment |
|
| Cholelithiasis | Hepatobiliary disorders | MedDRA version 8.1 | Systematic Assessment |
|
| Cystitis | Infections and infestations | MedDRA version 8.1 | Systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA version 8.1 | Systematic Assessment |
|
| Hypertensive Crisis | Vascular disorders | MedDRA version 8.1 | Systematic Assessment |
|
| Coronary Artery Disease | Cardiac disorders | MedDRA version 8.1 | Systematic Assessment |
|
| Head Injury | Injury, poisoning and procedural complications | MedDRA version 8.1 | Systematic Assessment |
|
| Road Traffic Accident | Injury, poisoning and procedural complications | MedDRA version 8.1 | Systematic Assessment |
|
| Wound | Injury, poisoning and procedural complications | MedDRA version 8.1 | Systematic Assessment |
|
| Pancreatic Enzymes Increased | Investigations | MedDRA version 8.1 | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA version 8.1 | Systematic Assessment |
|
| Cervix Carcinoma Stage 0 | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 8.1 | Systematic Assessment |
|
| Suicide Attempt | Psychiatric disorders | MedDRA version 8.1 | Systematic Assessment |
|
| Renal Failure | Renal and urinary disorders | MedDRA version 8.1 | Systematic Assessment |
|
| Tooth Extraction | Surgical and medical procedures | MedDRA version 8.1 | Systematic Assessment |
|
| Urinary Track Infection Bacterial | Infections and infestations | MedDRA version 8.1 | Systematic Assessment |
|
| Injection Site Reaction | General disorders | MedDRA version 8.1 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA version 8.1 | Systematic Assessment |
|
| Pharyngitis | Infections and infestations | MedDRA version 8.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA version 8.1 | Systematic Assessment |
|
| Urinary Track Infection | Infections and infestations | MedDRA version 8.1 | Systematic Assessment |
|
| Gingival Infection | Infections and infestations | MedDRA version 8.1 | Systematic Assessment |
|
| Dental Caries | Infections and infestations | MedDRA version 8.1 | Systematic Assessment |
|
| Respiratory Track Infection | Infections and infestations | MedDRA version 8.1 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA version 8.1 | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA version 8.1 | Systematic Assessment |
|
| Dental Operation | Surgical and medical procedures | MedDRA version 8.1 | Systematic Assessment |
|
| Blood and Lymphatic system disorders | Blood and lymphatic system disorders | Organ system | Systematic Assessment |
|
| Injury, poisoning and procedual complications | Injury, poisoning and procedural complications | Organ system | Systematic Assessment |
|
| Musculoskeletal and connective tissue disorders | Musculoskeletal and connective tissue disorders | organ system | Systematic Assessment |
|
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| D000081207 | Primary Immunodeficiency Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D014581 | Urticaria |
| D017445 | Skin Diseases, Vascular |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| D007153 | Immunologic Deficiency Syndromes |